Recently, a nonalcoholic fatty liver disease (NAFLD) is a growing medical problem in many countries, and may progress to an end stage liver disease. The feature of causing the NAFLD is without excess alcohol consumption, that is, the amount of alcohol intake is less than 20˜40 g ethanol for men and less than 20 g ethanol for women. The NAFLD refers to a wide spectrum of liver diseases comprising simple steatosis, nonalcoholic steatohepatitis (NASH) developed from steatosis, even cirrhosis, liver failure or a liver tumor developed from NASH.
Mitochondrion is a double membrane organelle existing in the cytoplasm of eukaryotic cells. According to different types of cells, hundreds to thousands of mitochondria are found. The mitochondrion is composed of compartments responsible for various specialized functions. These compartments include an inner membrane, an outer membrane, an intermembrane space, and a matrix. There are many inward folds called as cristae formed on the inner membrane. The cristae are studded with many proteins to use for aerobic respiration and to produce adenosine triphosphates (ATPs). The proteins producing ATPs are electron transport chain (ETC) enzymes including mitochondrial complex I to V (NADH dehydrogenase, succinate dehydrogenase, ubiquinol-cytochrome c oxidoreductase, cytochrome c oxidase, ATP synthase) for providing energy to cells.
Increasing oxidative stress in cells is an important pathophysiological mechanism of the NASH. In previous studies, free radicals are generated certainly from mitochondria in liver of a mammal. At normal physiological conditions, only 0.15% electrons are combined with oxygen to form superoxide anion radicals (O2.−). The O2.− is converted into hydrogen peroxide (H2O2) by manganese-superoxide dismutase (Mn-SOD), and then the H2O2 is converted into H2O and O2 by various anti-oxidative enzymes in cells. Once mitochondrial dysfunction is occurred, the O2.− production may be significantly increased to result in lipid peroxidation from polyunsaturated fatty acids, such that the formation of lipid peroxides, such as thiobarbituric acid-reactive-substance (TBARS), is increased. The half life of the lipid peroxides is longer than the half life of reactive oxygen species (ROS), and the lipid peroxides may be spread to the vicinity of the cells, thus amplifying the effects of the oxidative stress. However, in the process of transferring elections, O2.− is majorly formed via leaking an electron from mitochondrial complex I and III and coupling with oxygen.
Recently, the number of patients accepting the NAFLD treatment is small, and the tracking duration thereof is not very long. In previous studies, laboratory animals are fed with high calorie diets to induce the NAFLD, thereby imitating fat accumulation in a liver of a human. Simple steatosis is reversible, i.e. when the laboratory animals are without feeding a high calorie diet, the amount of fat in the liver thereof are decreased. Therefore, it is a difficulty to achieve liver inflammation.